Treatment of Advanced Breast Carcinoma with Drostanolone Propionate

'' is widely accepted that in cases of advanced breast cancer hormonal therapy can result in a temporary ?emission of symptoms with relief of pain and prolon9ation of life (Stott, 1959). Steroids, androgens, oestro93ns, castration, adrenalectomy and hypophysectomy ^ave all been used with some success, and it is Relieved now that a change in the hormonal environment of the tumour and its metastases is as likely to Produce a remission as any more specific treatment. Methods of determining if a tumour is hormone dependant have been investigated by Bulbrook (1964) ^ho described a method based on the urinary excretion of steroids. The observation that prolonged use of ap|drogenic hormones caused virilising effects led to l^e development of 2-alpha-methyldihydrotestosterone Propionate or drostanolone propionate (Masteril), which ls an androgenic hormone that does not produce sign'ficant virilising effects ('Blackburn and Childs, 1959). The clinical response to this hormone of a pre-menoPausal patient with painful bone secondaries is desCribed. This was the first occasion on which this drug was used in Britain for human therapy. case report Mrs. V. P., a fifty-five year old pre-menopausal lady pd a modified left radical mastectomy in June 1965, ?r a well differentiated mucus secreting carcinoma Without axillary gland involvement. She remained well Ur|ti| December 1967 when she developed pain in both 69s, and x-rays revealed osteolytic metastases in her Pelvis and femora. Treatment with drostanolone proP'onate 100 mg intra-muscularly every week was commenced in December 1967, and within two weeks her ?ain had completely disappeared. Pain recurred after 'Ve months, in the right leg, and x-rays demonstrated 'bespread lytic and porotic secondaries in the chest,

'' is widely accepted that in cases of advanced breast cancer hormonal therapy can result in a temporary ?emission of symptoms with relief of pain and prolon-9ation of life (Stott, 1959). Steroids, androgens, oestro-93ns, castration, adrenalectomy and hypophysectomy ^ave all been used with some success, and it is Relieved now that a change in the hormonal environment of the tumour and its metastases is as likely to Produce a remission as any more specific treatment.
Methods of determining if a tumour is hormone dependant have been investigated by Bulbrook (1964) ^ho described a method based on the urinary excretion of steroids. The observation that prolonged use of ap|drogenic hormones caused virilising effects led to l^e development of 2-alpha-methyldihydrotestosterone Propionate or drostanolone propionate (Masteril), which ls an androgenic hormone that does not produce sign'ficant virilising effects ('Blackburn and Childs, 1959).
The clinical response to this hormone of a pre-meno-Pausal patient with painful bone secondaries is des-Cribed. This was the first occasion on which this drug was used in Britain for human therapy. case report Mrs. V. P., a fifty-five year old pre-menopausal lady pd a modified left radical mastectomy in June 1965, ?r a well differentiated mucus secreting carcinoma Without axillary gland involvement. She remained well Ur|ti| December 1967 when she developed pain in both 69s, and x-rays revealed osteolytic metastases in her Pelvis and femora. Treatment with drostanolone pro-P'onate 100 mg intra-muscularly every week was commenced in December 1967, and within two weeks her ?ain had completely disappeared. Pain recurred after 'Ve months, in the right leg, and x-rays demonstrated 'bespread lytic and porotic secondaries in the chest, ^elvis, femora and lumbar spine. Bilateral  December 1967, was stopped at the time of the adrenalectomy. By July, 1969, although her foot drop had improved, she had developed lumbar and right scapular pain and showed the presence of painless skull secondaries. Drostanolone propionate was re-started, and within two weeks she was pain free in her back, shoulder and leg and there followed further improvement in her foot drop. Chest x-ray revealed barely detectable osteosclerotic metastases. In September 1969 roentgenography failed to show evidence of further skeletal metastases, her foot drop had disappeared and she was able to return to part time machine work. X-ray in January 1970 failed to show an increase in size in the metastatic deposits as compared with May, 1959. DISCUSSION Tagnon (1969 suggests that early in their development, metastatic deposits maintain a strong identity with the parent tissue and during this time are hormone-dependant. Later this identity is lost and the tumour cells become hormone-independent. Deshpandc; (1967) demonstrated that drostanolone propionate reduced the uptake of oestradiol-17B by tumour cells, whereas Altman and Chayen (1967) suggested that the drug acted by diverting the reduced co-enzyme NADPH into the metabolically wasteful diaphorase system thus limiting the amount of biosynthesis in the carcinoma.
Evidence that the cancer cells were hormone-dependent was suggested by the relief of bone pain after the administration of drostanolone propionate. Although the initial treatment failed to control the growth of secondary deposits, pain was relieved for some months. Oophorectomy caused a temporary osteosclerosis and a ten month remission from pain. After seventeen months of continuous treatment with drostanolone propionate there were no signs of masculinzation. Adrenalectomy relieved pain for two months, by which time there was evidence of further spread of osteolytic lesions. Within two weeks of re-starting drostanolone therapy, pain had again disappeared and the metastases started to become sclerotic. This case illustrates some interesting features which invite various suggestions.
(i) Drostanolone propionate can produce remission of pain in the presence of active ovaries, though it is specially recommended for the post menopausal patient. (ii) A trial period on drostanolone propionate suggested that the tumour cells were hormone dependent and is offered as a simple clinical way of determining this fact. (iii) Virilization was not a noticeable side effect. (iv) Axillary glands were not involved by tumour at the time of operation, yet distant spread had occurred.
This re-inforces the argument in favour of chemotherapeutic "cover" at the time of surgery and drostanolone propionate may prove a useful adjunct to surgery as such an agent.
(v) A febrile illness, such as influenza can produce a period of accelerated growth in bony metastatic deposits. This raises the question of immunology and demands that patients should be closely watched after such an illness.